吡咯烷二硫代氨基甲酸盐对兔脑血管痉挛的作用

Effect of pyrrolidine dithiocarbamate on cerebral vasospasm after subarachnoid hemorrhage in rabbits

目的观察吡咯烷二硫代氨基甲酸盐(PDTC)对兔蛛网膜下腔出血(SAH)后脑血管痉挛的影响及NF-κB p65、ICAM-1在基底动脉的表达。方法新西兰大白兔48只(雌雄不限)。随机分为对照组(8只)、SAH组(20只)及PDTC组(20只)。SAH组和PDTC组义分为SAH后1、3、5、7、14d亚组,每组4只。采用枕大池二次注血法制作SAH模型。PDTC组在第2次注血后即脑池内注射PDTC,0.25ml/次,2次/d,连续2d。观察基底动脉管径和厚度、病理形态学改变;免疫组化检测NF-κB p65、细胞间黏附分子1(ICAM-1)的表达。结果①SAH组在第3天开始出现基底动脉管径变细、管壁增厚,第7天最明显,与第1天比较,差异有统计学意义(P<0.05,P<0.01);PDTC组仅第7天与第1天比较有差异(P<0.05)。在第3、5、7天时,SAH组与对照组及PDTC组比较上述指标,差异均有统计学意义(P<0.05,P<0.01);PDTC组与对照组比较,差异均无统计学意义。②PDTC组与SAH组同时间点比较,病理形态损害、炎性细胞浸润程度减轻。③SAH组在第3天开始出现NF-κB p6、ICAM-1表达,第7天达高峰。第3、5、7 d(ICAM-1包括第14 d),SAH组表达量均明显高于对照组和PDTC组(P<0.01)。PDTC组与对照组比较亦增高,P<0.05。结论 PDTC对SAH后迟发性脑血管痉挛具有一定的预防作用。通过抑制NF-κB p65、ICAM-1的表达可能是其机制之一。

Objective To observe the effect of pyrrolidine dithiocarba-mate （PDTC） on cerebral vasospasm after subarachnoid hemorrhage （SAH） in rabbits and the expressions of NF-KB p65 and endothelial in- tercellular adhesion molecule-1 （ ICAM-1 ） in basilar arteries. Methods Forty-eight New Zealand white rabbits were randomly assigned into following three groups： sham operation group （n =8）, SAH group （n = 20）, and PDTC group （n =20）. The SAH and PDTC groups were redivided into day 1, 3, 5, 7, and 14 subgroups after SAH （n = 4 in each group）. The SAH model was induced by injection of autologous blood twice into cisterna magna. Intracisternal injection of PDTC, 0.25 mL, twice a day for 2 days was performed in the PDTC group. The diameter and thickness of the basilar artery, and the pathomorphological changes were observed. Immunohistochemistry were used to detect the expressions of NF-κB 1365 and ICAM-1. Results （1）The diameter of basilar artery began to become thin and its wall became thick from day 3 in the SAH group, and it was most obvious at day 7. As compared to day 1, there were significant differences （P 〈0.05, P 〈 0.01 ） ; there was only significant difference between day 7 and day 1 in the PDTC group （P 〈 0. 05 ）. The SAH group compared to the sham-operation and PDTC groups at day 3, 5, and 7, there were sig- nificant differences in the above indictors （ P 〈 0.05, P 〈 0.01 ） ; but there were no significant differences between the PDTC group and the sham operation group. （2）The pathological morphology and the degree of inflammatory cell infiltration were mild in the PDTC group as compared to the SAH group at the same time point. （3） The expressions of NF-κB p65 and ICAM-1 began to appear at day 3 in the SAH group, and reached to the peak at day 7, it was significantly higher than those in the sham operation and PDTC groups at day 3, 5, and 7 （ICAM-1 included day 14） （P 〈0.01）, and those in the PDTC group were higher than the sham operation group （P 〈 0. 05）. Conclusion PDTC has certain preventive effect on delayed cerebral vasospasm after SAH, inhibiting the expressions of NF-κB p65 and ICAM-1 may be one of its mechanisms.